This proposal is an application for renewal of support for the Oregon State University Environmental Health Sciences (EHS) Center. EHS Center funding supports EHS Center Investigators, core units, and enrichment programs. The administrative and facilities units are: Director's Office, Administration, Aquatic Toxicology, Bioanalytical Chemistry, Cell Culture, Flow Cytometry, Mass Spectrometry, Nucleic Acids and Proteins, Pathology, Statistics, Technical Services, and Pilot Projects. The units and their facilities' "state-of-the-art" equipment are utilized by the Director and Center Investigators to conduct research programs at the molecular, cellular, organ, and whole animal levels. The mechanisms of action of a variety of environmental chemicals including polyhalogenated hydrocarbons, pyrrolizidine alkaloids, mycotoxins, halogenated aliphatic hydrocarbons, as well as chemicals capable of formation of biological reactive intermediates and/or induction of biological processes are under investigation in Center Investigators' funded research. The theme of the research mission for the EHS Center is the effects of environmental chemicals on proteins, nucleic acids, and gene expression. The research activities will be devoted largely to (1) interactions of environmental agents with cellular macromolecules, (2) the effects of such agents on gene expression and the properties of gene products, and (3) the analytical tools with which to analyze the environmental agents and the nature of their interaction with macromolecules. The EHS Center Investigators' research interests include bioanalytical chemistry, mass spectrometry instrumentation development, biochemical toxicology, receptor proteins and their mechanisms, growth factors, mechanisms of cellular regulation and death, cellular defense systems, metabolism of environmental chemicals and toxicity, protein and DNA alkylation, gene expression, carcinogenicity mechanisms, modulation ofinitiation and promotion of carcinogenesis and immunotoxicology, and development of statistical methods. The research supported by the Program Project Grant "Toxicology of Environmental Halocarbons" (NIEHS ES00040) utilizes the core unit resources of the EHS Center, and the annual Pilot Project Program provides opportunities for development of new research activities, capabilities, and initiation of new collaborations. Training and enrichment programs through the affiliated NIEHS Training Grant and the M.S/Ph.D. Toxicology Program include various seminar programs at appropriate levels (academic and public), and workshops, a visiting scientists program, and a liaison with the Extension service toxicology program at OSU. The proposed EHS Center activities are designed to provide a base of support for research that will expand our knowledge about mechanisms of action of certain environmental agents. These efforts should enhance our ability to predict with greater assurance the human health risk due to exposure to these agents.